Zanidatamab Added to NCCN Guidelines for HER2+ Biliary Tract Cancer

Gastric/GEJ tumor: ©LASZLO - stock.adobe.com

Zanidatamab-hrii (Ziihera), a bispecific antibody targeting HER2, is now listed as a category 2A treatment option in the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of biliary tract cancer (BTC).¹

The agent recently received accelerated approval from the FDA for adult patients with previously treated, unresectable or metastatic HER2-positive BTC.² This approval was based on results from the HERIZON-BTC-01 clinical trial, which demonstrated a 52% objective response rate (ORR) and a median duration of response (DOR) of 14.9 months.^3,4

In the HERIZON-BTC-01 trial, a phase 2b open-label, multicenter study, 62 patients with HER2+ BTC who had previously received at least 1 gemcitabine-containing chemotherapy regimen were enrolled. Initial findings from the study were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. Here, a confirmed ORR of 41.3% was reported (95% CI, 30.4%-52.8%).

Updated results presented at the 2024 ASCO Meeting showed sustained outcomes with a median overall survival (OS) of 15.5 months (95% CI, 10.4-18.5). Higher OS rates were seen in patients with HER2 immunohistochemistry (IHC) 3+ (18.1 months; 95% CI, 12.2-23.2) vs IHC 2+ (5.2 months; 95% CI, 3.1-10.2).

The mechanism of action of zanidatamab involves binding to 2 extracellular sites on the HER2 receptor. This leads to tumor growth inhibition and cell death through complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis.¹ Zanidatamab is the first dual HER2-targeted bispecific antibody for BTC and offers a chemotherapy-free treatment option.

Looking at safety, the most common adverse events (AEs) seen in the study consisted of diarrhea, infusion-related reactions, abdominal pain, and fatigue.^3,4 Serious AEs occurred in 53% of patients, and biliary obstruction and biliary tract infections were the most frequently observed. Additionally, the overall safety profile was manageable; however, there were cases of severe reactions, with a small percentage of patients discontinuing the treatment due to AEs.

The approval of zanidatamab represents a significant advancement in the treatment of HER2-positive BTC. This approval is supported by promising clinical data, and ongoing confirmatory trials will be essential to further validate the clinical benefits.¹

Zanidatamab’s development is part of Jazz Pharmaceuticals' broader efforts to offer targeted treatment options for solid tumors expressing HER2, with ongoing trials evaluating its potential in other cancers, including gastroesophageal adenocarcinoma.¹ In addition, zanidatamab is also being explored in combination with other therapies, offering hope for more effective treatment regimens for patients with HER2-amplified cancers.

REFERENCES:

1. Jazz Pharmaceuticals announces update to National Comprehensive Cancer Network® (NCCN®) clinical practice guidelines in oncology for biliary tract cancers to include zanidatamab-hrii (Ziihera®). News release. Jazz Pharmaceuticals plc. December 5, 2024. Accessed December 5, 2024. https://tinyurl.com/bdduk9dr

2. Jazz Pharmaceuticals Announces U.S. FDA Approval of Ziihera® (zanidatamab-hrii) for the Treatment of Adults with Previously Treated, Unresectable or Metastatic HER2-positive (IHC 3+) Biliary Tract Cancer (BTC). Published online November 20, 2024. Accessed November 21, 2024. https://tinyurl.com/3vt9ka3b

3. Jazz Pharmaceuticals and Zymeworks Present Positive Pivotal Phase 2b Trial Data at ASCO 2023 Evaluating Zanidatamab in HER2-Amplified Biliary Tract Cancers. Published online June 2, 2023. Accessed December 5, 2024. https://tinyurl.com/4zud3edx

4. Pant S, Fan J, Oh D, et al. Zanidatamab in previously-treated HER2-positive (HER2+) biliary tract cancer (BTC): Overall survival (OS) and longer follow-up from the phase 2b HERIZON-BTC-01 study. J Clin Oncol. 2024;42(suppl 16):abstr 4091). doi:10.1200/JCO.2024.42.16_suppl.409